The regulatory mechanism for control of growth rate and differentiation of normal and neoplastic neuronal cells is poorly understood. Nerve growth factor (NGF) is a polypeptide important to the normal growth and development of the sympathetic nervous system of vertebrates. NGF can decrease the growth rate, induce neurite outgrowth, and enhance activity of enzymes regulating transmitter synthesis in rat pheochromocytoma (PC12) cells and in certain human neuroblastoma cell lines. The objective is to define the sequence of molecular events culminating in the differentiated state by studying binding of NGF, by identifying differentiation-specific macromolecular components (MC), by studying the pattern of MC in wildtype and NGF-resistant variants in the absence and presence of NGF, other agonists, and antagonists of neurite outgrowth. Attempts will be made to determine whether regulation of MC is at the transcriptional, translational or post-translational level. Binding of NGF to PC12 cells will be studied in culture and in vivo and will be compared with the properties of binding to rat adrenal chromaffin cells. Binding and response to NGF of cultured human neuroblastoma lines will be compared with that to freshly cultured tumors. There is weak circumstantial evidence suggesting involvement of NGF in neuronal tumors and this proposal is directed towards study and resolution of this possibility, as well as towards furthering the basic understanding of neuronal cell differentiation.